Clinicians reduced prescriptions for one second-generation
antipsychotic medication associated with metabolic problems after the
Food and Drug Administration required warnings in 2003 about increased
risk for diabetes and hyperlipidemia with that class of drugs, a new
study shows.

Clinicians did not increase metabolic testing, however, despite
recommendations issued at that time by the American Diabetes Association
(ADA) and the American Psychiatric Association (APA) to test glucose and
lipid levels in all patients who start a second-generation
antipsychotic, a large controlled study found. The study looked at
109,451 Medicaid recipients who started second-generation antipsychotic
medications, and a control cohort of 203,527 patients who began taking
albuterol but did not receive a second-generation antipsychotic.

Before the FDA warnings and the ADA/APA recommendations, 27% of
patients who started a second-generation antipsychotic underwent
baseline serum glucose testing, compared with 26% of control patients.
Clinicians got baseline lipid tests in 10% of patients starting a
second-generation antipsychotic and 11% of controls. The only
statistically significant change in testing rates during or after
issuance of the warnings and guidelines was a clinically insignificant
2% increase in baseline lipid testing in patients starting a
second-generation antipsychotic, Elaine H. Morrato, Dr.P.H., and her
associates reported (Arch. Gen. Psychiatry 2010;67:17-24).

Previous studies have shown that the warnings produced no
clinically meaningful change in glucose and lipid monitoring in
commercially insured patients. The current retrospective cohort study is
the first to find a similar pattern in a Medicaid population, reported
Dr. Morrato of the University of Colorado, Denver.

The FDA compelled drug manufacturers to change labels for
second-generation antipsychotics starting in December 2003 and to mail
"Dear healthcare professional" letters to neuropsychiatry health care providers through August 2004 to warn of increased risk for
hyperglycemia and diabetes with use of second-generation antipsychotics
and to recommend monitoring of glucose levels in patients with diabetes,
risk factors for diabetes, or hyperglycemia. Concurrently, ADA and APA
consensus statements described the metabolic risks of second-generation
antipsychotics and provided a monitoring protocol that included baseline
tests of glucose levels and lipid profiles.

The current study used data from patients in California, Missouri,
and Oregon during a prewarning period (January 2002 through November
2003), a warning period during which the letters were mailed and the
ADA/APA recommendations came out (December 2003 through August 2004),
and a post-warning period (September 2004 through December 2005).
Prescriptions for clozapine were excluded because of the drug's
unique requirement for neutropenia-related testing.

The warnings and recommendations did not increase rates of
metabolic testing in patients starting second-generation antipsychotics,
but clinicians did reduce their use of olanzapine, which would be
consistent with intent to reduce metabolic risk, the investigators
noted. Before the FDA warnings, olanzapine use was already declining by
5% per year, compared with other second-generation antipsychotics;
during the warning period, olanzapine use declined by 20% per year. Use
of a second-generation antipsychotic with lower metabolic
risk--aripiprazole--increased significantly during the warning period
but not the post-warning period, a change that might have been
attributable more to California's elimination of the need for prior
authorization for aripiprazole prescriptions during that time than to
concerns about diabetes and hyperglycemia, Dr. Morrato and her
colleagues suggested.

The FDA warnings and ADA/APA recommendations did not affect the use
of quetiapine, ziprasidone, or risperidone.

People with serious mental illness are 1.5-2 times more likely to
develop dyslipidemia, hypertension, obesity, and type 2 diabetes
mellitus, compared with the general population. More effort is needed to
increase screening for diabetes and dys-lipidemia in patients receiving
second-generation antipsychotics and monitoring for metabolic side
effects of these drugs.

In some previous studies, 60%-80% of psychiatrists reported that
they do regularly monitor glucose and lipid levels in patients taking
second-generation antipsychotics, and two-thirds of community mental
health centers reported having protocols or procedures to screen for
diabetes and dyslipidemia. More research is needed to understand the
discrepancy between these reports and the low rates of screening found
in the current study.

Disclosures: Funded by Pfizer, which makes ziprasidone. The
investigator has received research funds from Eli Lilly, maker of
olanzapine. Several other investigators have received funding from or
been consultants to those and other companies that make
second-generation antipsychotics.

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